If you’re reading this article, you probably already know what tyramine intolerance is. You probably also know I have it, and devote at least a certain amount of blogging time to exploring this health topic.
I’ve wanted to write a series on genes and tyramine intolerance. I cover some of this in my book, The Tyramine Intolerance Handbook, but this blog allows me to explore much more, especially as I learn more over time. And… it makes sense to begin with the gene that codes for the most important enzyme involved in the metabolism of tyramine:
Monoamine oxidase A, or MAO-A
But first, a quick primer on why we even talk about genes when it comes to food sensitivity.
Why are Genes Important in Tyramine Intolerance?
Our genes influence everything about us: our appearance, our behavior, and our health. They also play a significant role in food intolerance or sensitivity (not to be confused with food allergy). Why is this?
Food intolerance occurs when the body can’t effectively break down some substance in the foods you eat. The common example I often use is lactose intolerance, the inability to break down lactose, a type of sugar found in milk and dairy products.
But what breaks down lactose? An enzyme called lactase. If there isn’t enough lactase to break down lactose, you get symptoms.
Likewise, tyramine gets broken down by enzymes as well. And when you don’t have enough of those enzymes? Tyramine doesn’t get metabolized properly and that’s when the headaches, blood pressure spikes, palpitations, and anxiety kick in.
But where do enzymes come from? Your DNA, or genes.
We all have the same genes, but we inherit different “versions” of those genes from our biological parents. One gene can have numerous versions, or variants, and each variant will produce a slightly different product… in this case, an enzyme.
Different enzymes perform differently. If the enzyme your body produces functions less efficiently than normal, it can cause problems.
Monoamine Oxidase (MAO)
Of all the genes involved in tyramine metabolism, monoamine oxidase (MAO) plays the largest role, as far as we know. It’s the most discussed enzyme when the topic of tyramine comes up.
MAO is a well-known enzyme in the science world, but not because of its role in tyramine metabolism. MAO also breaks down many “monoamine” neurotransmitters in the body, including serotonin, dopamine, epinephrine, and norepinephrine, which makes it a big player in behavior and especially mental health.
Interestingly, MAO breaks down phenylethylamine (PEA), another amine found in high concentrations in chocolate.
The MAO enzyme actually has two slightly different versions, MAO-A and MAO-B (called isozymes in the science world). Likewise, we have an MAO-A gene and an MAO-B gene. Today, we’ll focus on MAO-A.
The Monoamine Oxidase (MAO-A) Gene
If you have a less efficient variant of the MAO gene, it may put you at higher risk for tyramine intolerance, and other things as well.
There are many ways genes that genes can produce different variants. The best known are SNPs, or single nucleotide polymorphisms. This is a genetic variant that differs by only ONE nucleotide.
If you want to investigate your genes in the context of your health, or understand your 23andMe or similar data, you’ll be investigating SNP data. For a good primer on SNPs, read this.
A given gene can have many different SNPs. If a gene is important in health, science will often investigate many SNPs in one gene to see if they’re associated with disease.
It just so happens that there are several SNPs in the MAO-A gene that scientists have studied at one time or another. Four of them are available in your 23andMe data.
For each SNP, a certain genotype leads to a “low activity” enzyme. And with tyramine intolerance, lower activity may mean slower metabolism of tyramine, which can lead to symptoms.
Let’s look at each of these SNPs, one at a time. I got some of this information from GeneFood, which has an MAO-A page.
rs6323
With this well-studied MAO-A SNP, the G variant results in an enzyme showing typical activity, whereas T results in reduced MAO-A activity. Therefore, since you inherit two copies:
G/G = typical MAO-A activity
G/T = somewhat reduced MAO-A activity
T/T = more reduced MAO-A activity
**Keep in mind that males, who only have one X chromosome, will have one SNP, not two like I’ve listed here.
One study found that the T variant was linked to migraine (PMID 22193458). For more info on this SNP, check out Genetic Lifehacks and SNPedia.
rs1137070
For this SNP, the risk allele is T, which codes for a reduced-activity variant. So,
C/C = typical MAO-A activity
C/T = somewhat reduced MAO-A activity
T/T = very reduced MAO-A activity
rs3027399
The risk allele for this SNP is G. So,
C/C = typical MAO-A activity
C/G = somewhat reduced MAO-A activity
G/G = very reduced MAO-A activity
rs909525
The risk allele for this SNP is C. So,
T/T = typical MAO-A activity
C/T = somewhat reduced MAO-A activity
C/C = very reduced MAO-A activity
Other SNPs
There are other MAO-A SNPs of interest as well. One study found that having a C at rs2072743 and a G at rs3027400 was associated with migraine.
My MAO-A Genotypes
| SNP | Genotype | MAO-A activity |
| rs6323 | TT | Very reduced |
| rs1137070 | CC | Normal |
| rs3027399 | GG | Very reduced |
| rs909525 | CT | Somewhat reduced |
Could my MAO-A SNPs be contributing to my tyramine intolerance? This would suggest yes. However…
Genes are Complicated
Keep in mind that when it comes to tyramine intolerance, monoamine oxidase A (and these SNPS) are only part of the story. Why?
Most people who develop tyramine intolerance don’t do so until they hit middle age. I’m no exception. Our genes don’t change, which means something else has influenced MAO-A activity and the ability to metabolize tyramine.
Also, other genes influence tyramine metabolism as well, which I will cover in other articles. Finally, other factors probably play an important role here, such as gut health. We have enzymes and neurons in the gut too, which could influence tyramine metabolism and the development of symptoms.
Just as importantly, genes are unpredictable creatures. Even if genotype GG in SNP X is associated with syndrome Y, there will always be people with syndrome Y who don’t have GG, and people with GG who don’t have syndrome Y.
But it’s still good to know as much as we can about tyramine intolerance and begin adding more pieces to the tyramine intolerance puzzle.
In the next article, we’ll talk about MAO-B.
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Related Articles
Tyramine Intolerance vs. Histamine Intolerance
The Tyramine Intolerance Handbook by Dr. Christie Hartman
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11 thoughts on “Genes and Tyramine Intolerance Part 1: Monoamine Oxidase A”
https://www.ncbi.nlm.nih.gov/snp/?term=rs1137070 reports major allele of T
https://www.ncbi.nlm.nih.gov/snp/?term=909525 reports a major allele of C
Those are the minor alleles. Look at the MAFs (minor allele frequencies) for each and you’ll see.
Thanks! You can see that I am a beginner… Where do I find the major allele?
If you look at MAF for the SNP, click on the ALFA link, and you’ll see allele frequencies for both in various populations.
For rs6323, I see that the ALFA trial shows ref allele G with 29% of the European population and alt allele of T with 7% of the European population. It also displays G>T, which I assumed to mean ref G and alt T.
For rs3027399, ALFA shows ref allele G with 93% and alt allele C with 6.7%. I also shows G>C, which I assumed to mean ref G and alt C.
With that, your genotype of TT for rs6323 would be a 7% (rare) alternate variant, but your genotype of GG for rs3027399 would be very much mainstream at 93%, and not “very reduced MAO A activity”.
For rs1137070, your genome of CC would be a 70% alt allele where T would be a 29% ref allele.
For rs1137070, your genome of CC would be a 70% alt allele where T would be a 29% ref allele.
What type of physician would be able to help me wade through my genetic data so I can address issues with MAO-A, MTHFR, or other genetic issues which may be impacting my health? It seems like this should be an established practice but none of my physicians past or present have ever looked at me from a genetic viewpoint. 🙂 Thanks!
Matt: I would look into a “functional medicine” doc or a nutritionist/dietician with that knowledge.
Hi Dr Hartman,
I’m grateful for your work in making this research more accessible to someone like me.
I have MSc in Plant genetics but it’s been a while since I did anything scientific so I don’t know the tools/resources.
I’m tyramine sensitive, from birth, presumably, certainly by 3 years old. I’m that exception. Sorry!
In many ways I think it might have been almost kinder that it didn’t wait and pounce on me later. I had a very plastic and adaptable worldview when I first had to contend with it.
I plan to get genotyped, for as much as that’ll tell me. Maybe volunteer for research.
I’m coming round to the idea that my tyramine intolerance is a useful diagnostic as well as a pathology.
Since discovering the names of the three genes of interest, I’ve had lots of fun reading about various substrates and associated traits.
I found your book and read it in the last week, too.
Well-written and useful. I think it could do with a certain aspect of context/perspective. There’s probably some appalling experiment that measures pain/suffering in rats that could place tyramine in some metric comparison to a frozen shoulder, or whatever.
But I’m trying to make a serious point.
For example I wish I could go back to myself at that tender age with a thumper, diarrhoea and grisly paisley patterns, and explain that “this is as bad as it gets. It’s battlefield-level suffering. Most people don’t know and that’s okay. Most of the time, I don’t remember how bad it is, and that’s okay too.”
Anyway I hope to help somehow with getting this pathology out there and understood.
I feel that there’s a tidal wave of research coming in this tyramine/dopamine biochemical network.
Please consider me for proofreading jobs or help with drafting etc.
My last job was Science Writer at a Genetics Institute, but sadly it was pitched right in the middle of a political and ideological split between researchers and executives, which required more patience and tact than I can muster day after day, week after week.
Regards
Nigel
Thanks for commenting, Nigel. I’ve seen your posts on the FB group and am glad you’re looking into this from a scientific perspective. If we all put our heads together, maybe we can figure it out.